Scleroderma (PSS) is not a benign disease and is associated with high mortality and morbidity. Until very recently there has been remarkably little progress in the treatment of this disease. A number of drugs have been studied but none have been shown to be efficacious. Over the last 9 years we have been involved in a double-blind, parallel, study of chlorambucil versus placebo in which each patient is on the study drug for 3 years. At the present time we have enrolled 70 patients. The quality of the data generated from this study has resulted in the publication of 18 descriptive articles and the preparation of several more. These publications attest to our ability to maintain the quality of the data. Further, we have been able to maintain the double-blind nature of the study. We propose, in this application, to analyze the results of this study. Using statistical techniques such as chi-square analysis, t statistics, ANOVA, covariance analysis, multi-variate techniques and power analysis, we will examine outcome measures such as mortality, failure or drop out rates, differences in functional outcome and changes in individual and combined measures of visceral function over time. At the end of the 2 years required for this analysis we will: 1) have evaluated the efficacy of Chlorambucil in stablizing and/or improving PSS; 2) have evaluated the reliability and sensitivity of a set of measurements which objectively measure changes in PSS activity; 3) hope to have developed prognostic indicies to predict which patients could most benefit from this drug therapy.